How to Vaccinate the World (Next Time)

Booth’s John R. Birge has been researching the drug development process in the US for more than a decade with an eye toward speeding it up. In research published in 2016, he and Southern Methodist University’s Vishal Ahuja (a graduate of Booth’s PhD Program) recommended cutting the drug approvals timeline by using adaptive trials, which would adjust the number of patients randomly assigned to treatment groups as information emerged about a drug’s effectiveness. (To learn more, read “How math can improve drug trials and save lives.”)

But the expedited greenlighting of the COVID vaccine indicates that the conventional final stage of approvals could be scaled back and combined with better postmarket surveillance after a drug’s public release, some of their more recent work suggests. Ahuja, Texas Tech’s Carlos Alvarez, Birge, and Booth’s Chad Syverson find that the relative lack of data collection that is necessary to speed vaccine approval could be remedied by conducting more rigorous surveys. “The FDA should be exhaustively canvassing vaccinated people to see what the severe adverse events have been, as opposed to the voluntary system we have now,” Birge says.

Their study looks at the diabetes drug rosiglitazone to determine whether the method that the FDA uses to assess and announce safety risks that arise after the agency has already approved a drug for use can hurt patients by scaring them away from treatment unnecessarily. In the case of rosiglitazone, after it was approved and released, studies linked the drug to heart problems. The FDA, in line with its current practice, kept the drug on the market but issued a warning designed to call attention to life-threatening risks. Consequently, most doctors and patients dropped the drug, and few resumed using it even after additional studies indicated the drug was safe and the FDA eliminated its warning.

While the FDA was seeking to keep patients apprised of newly identified health risks, it ended up deterring many people who would have benefited from using the drug, argue the researchers, who identify several weaknesses in the agency’s postmarket surveillance systems that can cause high error rates. They propose an approach grounded in statistics and economics that the FDA could use to independently validate any safety signals and better catch and assess risks that do turn up. (For more about this research, read “A new approach to ensuring drugs are safe.”)

The same issues surrounding data collection apply to the rollout of the COVID vaccine, Birge notes. The FDA is not currently collecting information needed to adequately assess the side effects of each COVID vaccine, even though the safety bar was lowered significantly in order to expedite vaccine approvals. “The current system is effectively anecdotal and does not systematically try to assess whether serious adverse events are occurring in those who are treated,” he says.

And beyond the coronavirus, combining long-term data collection with adaptive trials conducted before a drug’s release could cut years from the approvals process, he adds. It could slash the cost of development and save untold lives by bringing critical medicines to market faster. Thus, some regulatory changes inspired by this pandemic could potentially lead to better outcomes in a future pandemic, and in more normal times too.

Lesson #2: Partner with pharma companies to build capacity faster

After COVID vaccines began to be approved in late 2020, the industry responded quickly, producing 11.2 billion doses in 2021. Today, wealthy countries have more than 1 billion surplus vaccine doses.

But had the industry increased supply even faster, the US might have achieved widespread vaccination four months earlier than it did (in March 2021 rather than July 2021), and more of the rest of the world might be vaccinated too, according to research by a team including Chicago Booth’s Eric Budish and Canice Prendergast. (For more, read “Why the world needs a lot more vaccine capacity.”) A few months may sound insignificant, but the researchers, drawing on calculations by Harvard’s David M. Cutler and Lawrence H. Summers, estimate the global harm wrought by the pandemic to have been about $1 trillion a month until vaccination started.

The key to a better ramp-up, Budish says, is more government outlay and a genuine partnership with the companies that invent vaccines. Essentially, Budish thinks the world, and rich countries in particular, should have invested more, earlier in working with companies to construct production facilities that might never have come online. Early on in the pandemic, the US initially headed in this direction but was ultimately too timid and invested only around one-tenth of what was likely necessary, he says, while other countries did even less. Had governments put more money into this “capacity at risk,” pharmaceutical companies could have had more factories ready to go as soon as their vaccine was approved. Given the high price of the pandemic, this added speed would have warranted the cost to the US and other governments of potentially paying for redundant capacity.

Then, says Budish, once vaccines were shown to work, governments should have invested exponentially more in production and distribution. Rather than discussing whether to seize intellectual property and waive patents—a conversation that he views as an excuse to avoid spending—countries should have been challenging companies to work with them to vaccinate the world fast. Budish notes that at a rough price of $50 per shot, vaccinating 5 billion people worldwide costs $250 billion. As governments have to spend that money anyway, he would have preferred that figure to have been used up front as an incentive to pharmaceutical companies to build production capacity on an industrial scale.

“The conversation I wish had happened was, ‘We would like to vaccinate the world in six months, with 5 billion courses of mRNA. Please submit some proposals—and we’re willing to pay up to $250 billion for it,’” he says. “You might get nothing credible, but then you at least learn what’s possible.”

Adopting a problem-solving partnership with pharmaceutical companies could, Budish suggests, prove a more efficient and effective path to vaccinating large numbers of people next time we need to do so.

Lesson #3: Focus on the social benefits

During the pandemic, vaccines took on a political significance in the US as never before. While some Americans posted images of their vaccination cards online, others railed against vaccine mandates. Some expounded elaborate conspiracy theories about government tracking devices being implanted in unwary people.

But vaccine hesitancy, rather than vaccine rejection, perhaps better explains the slow uptake of inoculation. Only 12–16 percent of US residents said over the past year that they would “definitely not” get vaccinated, according to an ongoing monthly Kaiser Family Foundation survey. Many people found themselves in the middle, wary of fake news but unsure about the vaccine’s safety. Between February 2021 and February 2022, the percentage saying they would get vaccinated only if required to do so shrank from 7 percent to 3 percent, and the “wait and see” crowd fell from 22 percent to 4 percent of the population.

One reason for vaccine hesitancy cited by many scholars is higher-than-average levels of distrust in the government and medical profession among the US’s Black and Hispanic communities. Many observers trace this to unethical medical episodes such as the infamous Tuskegee experiments of 1932–72, in which Black men infected with syphilis were recruited on the promise of free medical care but were then deliberately denied treatment and given placebos. Vaccine hesitancy among historically marginalized groups is particularly concerning since COVID disproportionately hits these communities in the US.

More generally, elevated concerns about vaccine safety were perhaps predictable given the accelerated approvals process. Omission bias is a behavioral tendency that favors doing nothing over taking an action that is potentially harmful, even when doing nothing is also harmful. Worried that getting inoculated for COVID is riskier than taking a medicine approved via the conventional route, many people have opted to go unvaccinated.

Identifying and addressing the appetite for risk in this context could help reduce vaccine hesitancy, according to research by Vanderbilt’s Jennifer S. Trueblood, Booth’s Abigail Sussman, and Booth postdoctoral scholar Daniel O’Leary. The researchers find a correlation between financial-risk aversion and vaccine hesitancy. The more appetite participants in their study had for financial risk, the more likely they were to be open to getting vaccinated. (For more on this research, read “Financial-risk preferences predict vaccine acceptance.”)

In the second part of their paper, the researchers found a way to sway more risk-averse people—by reframing the issue in terms of the social and communal benefits of vaccines rather than as one of individual risk. They randomly assigned 1,003 online participants, recruited from Amazon’s Mechanical Turk, to read one of four messages about a hypothetical COVID vaccine. Participants in a control group received general information about the FDA’s vaccine approval process and the vaccine’s efficacy and potential side effects. Those in the other groups received the same information, as well as further details that stressed either the individual benefit of getting vaccinated, the social benefit, or both.

After reading, participants reported how soon they would be willing to take the vaccine once it became available. Those whose attention had been focused on the community were willing to get the shot significantly sooner.

Sussman says that while the researchers didn’t track official public-health announcements during the pandemic, her sense is that messaging campaigns tended to focus on individual rather than social benefits. For example, the Centers for Disease Control and Prevention page explaining the benefits of vaccination focuses on communicating that the COVID vaccine is a safe and effective way to build protection against the virus for oneself. Sussman says, “For the most part, they’re trying to solve for community-level outcomes, but they’re talking about individual-level risk. There’s a mismatch between the solution they are targeting and what they are communicating.”

The research suggests that focusing more on social benefits in public-health messaging could help to reduce vaccine hesitancy when we face future outbreaks.

Lesson #4: Pay people to take the shot

Aside from tweaking the message, a key way to help people overcome their fears may simply be to pay them to receive the vaccine, as many countries, cities, and states have done around the globe.

Early on in the pandemic, economists suggested paying people a significant sum to get vaccinated. Robert E. Litan, a nonresident senior fellow at the Brookings Institution, proposed giving Americans $1,000 each to get vaccinated. His proposal was backed by Harvard’s N. Gregory Mankiw in a New York Times op-ed.

But critics said the plan would be perverse and coercive. “It is deeply problematic that the government would offer cash incentives to promote vaccination when it has failed, in numerous instances throughout this pandemic, to offer money or other supports needed to ensure that the basic needs of many people are being met,” argued Emily A. Largent of the University of Pennsylvania Perelman School of Medicine and Franklin G. Miller of Weill Cornell Medical College in January 2021.

While the $1,000 payment was never implemented, a patchwork of pay-to-vaccinate schemes developed across the US. West Virginia paid some of its residents $100 to get a shot, Maryland did the same for state employees, and Colorado paid $500 to Department of Corrections employees who got fully vaccinated. Dozens of states offered tickets for lotteries with prizes ranging from millions of dollars in cash to free college tuition and luxury vacations.

Research by a team including Chicago Booth’s Devin G. Pope suggests that these large sum payments would have been effective and, in fact, even a small amount of money can demonstrably increase willingness to be vaccinated. Among a group of 8,300 participants in Sweden from May to July 2021, vaccination rates went from 72 percent to 76 percent after a 200 kronor payment (approximately US$24) incentivizing participants to get one shot. The increase was seen across socioeconomic groups. The research also tested whether behavioral “nudges” could boost rates and find that although these increased participants’ intention to get vaccinated, they didn’t have a meaningful effect on actual vaccination rates. (For more on this research, read “Does paying people to get vaccinated work?”)

Pope’s research touches on a long-standing debate in psychology and economics over the use of financial incentives to shape behavior. Essentially, critics of paying people to perform an action have argued that these payments could backfire by damaging people’s intrinsic motivation. Once people start to associate an activity with earning money, they think about it in a different way, and if the money is removed, they may be reluctant to continue the activity unless they are paid again, a critique psychologists term motivation crowding theory. Donors paid to give blood, for example, may stop doing so if the payments are halted, even if they might have previously given blood without getting paid.

But others argue the situation is more nuanced—for example, it’s possible a person donating blood may stop doing so, but only temporarily. (For more on this concept, read “Short-term rewards don’t sap long-term motivation.”)

In further research that studies paying people to get vaccinated, Pope and his coauthors quash any concerns about crowding out the desire to get a second shot. The researchers find that the people who were paid to get vaccinated in the first Swedish study were even more likely than average to receive a second vaccination shot, even though they were no longer paid for it.

To Pope, this is evidence that concerns over the unintended consequences of paying people to get vaccinated may be overblown. “My take from both our paper and the broader literature on using financial incentives to motivate healthy and prosocial behavior is that it almost never backfires,” Pope says.

This is not to say that financial incentives always work. Pope and Booth’s Richard H. Thaler (a Nobel laureate) were part of a team of researchers led by University of Pennsylvania’s Katherine L. Milkman that tested whether offering lottery tickets for vaccinations could raise inoculation rates. They set up three geographically targeted lotteries of up to $50,000, but find that the prizes did not significantly nor sustainably raise vaccination rates.

Instead, Pope says, consistent and relatively small universal payments could help keep the coronavirus under control, since regular booster shots are certain to be part of the solution. “Offering people $100 every year if they take their booster, that would have a pretty big effect,” he says. It’s a strategy officials could implement in the future—or right now.